Computational and Mathematical Methods in Medicine
Volume 2012 (2012), Article ID 805827, 15 pages
Review Article

Analyzing Effects of Naturally Occurring Missense Mutations

1Computational Biophysics and Bioinformatics, Department of Physics and Astronomy, Clemson University, SC 29634, USA
2Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, Inserm UMR-S 973, 35 rue Helene Brion, 75013 Paris, France

Received 21 December 2011; Revised 1 February 2012; Accepted 1 February 2012

Academic Editor: Gabriela Mustata Wilson

Copyright © 2012 Zhe Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well.